Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Stitz, R; Stoiber, F; Silye, R; Vlachos, G; Andaloro, S; Rebhan, E; Dunzinger, M; Pühringer, F; Gallo, C; El-Heliebi, A; Heitzer, E; Hauser-Kronberger, C.
Clinical Implementation of a Noninvasive, Multi-Analyte Droplet Digital PCR Test to Screen for Androgen Receptor Alterations.
J Mol Diagn. 2024; 26(6):467-478
Doi: 10.1016/j.jmoldx.2024.02.009
Web of Science
PubMed
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FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Heitzer Ellen
- Co-Autor*innen der Med Uni Graz
- Andaloro Silvia
- El-Heliebi Amin
- Vlachos Georgios
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- Abstract:
- Alterations of the androgen receptor (AR) are associated with resistance to AR-directed therapy in prostate cancer. Thus, it is crucial to develop robust detection methods for AR alterations as predictive biomarkers to enable applicability in clinical practice. We designed and validated five multiplex droplet digital PCR assays for reliable detection of 12 AR targets including AR amplification, AR splice variant 7, and 10 AR hotspot mutations, as well as AR and KLK3 gene expression from plasma-derived cell-free DNA and cell-free RNA. The assays demonstrated excellent analytical sensitivity and specificity ranging from 95% to 100% (95% CI, 75% to 100%). Intrarun and interrun variation analyses revealed a high level of repeatability and reproducibility. The developed assays were applied further in peripheral blood samples from 77 patients with advanced prostate cancer to assess their feasibility in a real-world scenario. Optimizing the reverse transcription of RNA increased the yield of plasma-derived cell-free RNA by 30-fold. Among 23 patients with castration-resistant prostate cancer, 6 patients (26.1%) had one or a combination of several AR alterations, whereas only 2 of 54 patients (3.7%) in the hormone-sensitive stage showed AR alterations. These findings were consistent with other studies and suggest that implementation of comprehensive AR status detection in clinical practice is feasible and can support the treatment decision-making process.
- Find related publications in this database (using NLM MeSH Indexing)
- Humans - administration & dosage
- Receptors, Androgen - genetics
- Male - administration & dosage
- Biomarkers, Tumor - genetics, blood
- Aged - administration & dosage
- Prostatic Neoplasms - genetics, diagnosis
- Reproducibility of Results - administration & dosage
- Mutation - administration & dosage
- Sensitivity and Specificity - administration & dosage
- Middle Aged - administration & dosage
- Cell-Free Nucleic Acids - genetics, blood
- Kallikreins - blood, genetics
- Prostatic Neoplasms, Castration-Resistant - genetics, diagnosis, blood
- Multiplex Polymerase Chain Reaction - methods